US7655641B2ExpiredUtilityPatentIndex 60
Sulfonamide derivatives as PPAR modulators
Est. expiryFeb 14, 2023(expired)· nominal 20-yr term from priority
Inventors:CONNER SCOTT EUGENEGOSSETT LYNN STACYGREEN JONATHAN EDWARDJONES JR WINTON DENNISMANTLO NATHAN BRYANMATTHEWS DONALD PAULMAYHUGH DANIEL RAYSMITH DARYL LYNNVANCE JENNIFER ANNWANG XIAODONGWARSHAWSKY ALAN MWINNEROSKI JR LEONARD LARRYXU YANPINGZHU GUOXIN
A61P 3/06A61P 3/10A61P 9/12A61P 9/04C07C 311/19C07C 2601/02C07C 311/29C07D 215/36C07D 263/32C07D 413/04A61K 45/06C07D 333/62C07D 213/74A61P 3/04C07C 2601/14C07C 323/49C07D 319/18C07D 307/79C07C 317/14C07C 2601/08A61K 31/00C07D 209/48C07C 323/52C07D 277/36C07D 307/82C07D 271/12C07D 409/04C07D 209/08C07D 333/34C07D 213/64C07D 213/71C07D 409/12C07D 207/08C07C 311/13C07D 231/18C07D 231/12C07C 311/17
60
PatentIndex Score
5
Cited by
41
References
19
Claims
Abstract
The present invention is directed to a compound of Formula (I): and pharmaceutically acceptable salts, solvates, hydrates or stereoisomers thereof, which are useful in treating or preventing disorders mediated by a peroxisome proliferator activated receptor (PPAR) such as syndrome X, type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to syndrome X and cardiovascular diseases.
Claims
exact text as granted — not AI-modified1. A compound having a structural Formula I,
or pharmaceutically acceptable salts or stereoisomers thereof,
wherein:
E is selected from the group consisting of O, S and NR 14 ;
W is selected from the group consisting of
hydrogen, C 1 -C 6 alkyl, (CH 2 ) n′ C 3 -C 6 cycloalkyl, haloalkyl and acyl;
Q is: —C(O)OR 6 or R 6A ;
X is selected from the group consisting of a bond, CH 2 , O, S and S[O] p ;
Y is selected from the group consisting of a bond, S, CH 2 and O;
Z is: benzothiophene;
wherein the benzothiophene is optionally substituted with one or more groups independently selected from R 15 ;
m and n′ are each independently selected from the group consisting of 0, 1, 2, 3 and 4;
n is selected from the group consisting of 0, 1, 2 and 3;
p is: 1 or 2;
r is selected from the group consisting of 1, 2, 3 and 4;
v is: 1 or 2;
R 1 is selected from the group consisting of hydrogen,
haloalkyl,
C 1 -C 6 alkyl,
C 1 -C 6 alkyl-C 1 -C 6 alkoxy,
C 1 -C 6 alkyl-aryl,
C 2 -C 6 alkenyl,
C 2 -C 6 alkynyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
C 1 -C 6 alkoxy,
aryl, and
R 1 and R 2 together being a 5- to 8-membered heterocyclyl ring;
wherein alkyl, aryl, alkenyl, alkynyl, cycloalkyl and alkoxy being optionally substituted with one or more groups independently selected from R 15 ;
R 1a and R 1b are each independently is selected from the group consisting of
hydrogen,
C 1 -C 6 alkyl, and
R 1 and R 1a , R 1 and R 1b , R 2 and R 1a , R 2 and R 1b or R 1a and R 1b together being a 3- to 6-membered heterocyclyl or carbocyclyl ring wherein at least one of R 1a and R 1b is not hydrogen;
R 2 is selected from the group consisting of hydrogen,
haloalkyl,
C 1 -C 6 alkyl,
C 1 -C 6 alkyl-C 1 -C 6 alkoxy,
C 1 -C 6 alkyl-aryl,
C 2 -C 6 alkenyl,
C 2 -C 6 alkynyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
C 1 -C 6 alkoxy,
aryl, and
R 1 and R 2 together being a 5- to 8-membered heterocyclyl ring;
wherein alkyl, aryl, alkenyl, alkynyl, cycloalkyl and alkoxy being optionally substituted with one or more groups independently selected from R 15 ;
R 2a is selected from the group consisting of hydrogen, halo, C 1 -C 6 alkyl and wherein R 2 and R 2a together being a 3- to 8-membered ring; wherein alkyl being optionally substituted with one or more groups independently selected from R 15 ;
R 3 is selected from the group consisting of hydrogen,
halo,
cyano,
haloalkyl,
C 1 -C 6 alkyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
(C 1 -C 4 alkyl)-heterocyclyl, and
(C 1 -C 4 alkyl)-NR 7 C(O) p R 9 ;
wherein alkyl, cycloalkyl and heterocyclyl being optionally substituted with one or more groups independently selected from R 15 ;
R 4 and R 5 are each independently selected from the group consisting of
hydrogen,
halo,
C 1 -C 6 alkyl
C 1 -C 6 alkoxy;
aryloxy;
N(R 8 ) 2 ,
SR 8 and
R 4 and R 5 together being a 3- to 8-membered ring;
R 6 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl and aminoalkyl;
R 6A is selected from the group consisting of carboxamide, C 1 -C 3 alkylnitrile, sulfonamide, acylsulfonamide and tetrazole;
R 7 is selected from the group consisting of hydrogen and C 1 -C 6 alkyl;
R 8 and R 9 are each independently selected from the group consisting of
hydrogen, C 1 -C 6 alkyl, aryl, heteroaryl, and heterocyclyl;
wherein aryl, heteroaryl and heterocyclyl being optionally substituted with one or more substituents selected from the group consisting of hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, oxo, C 1 -C 6 alkyl and C 1 -C 6 alkoxy;
R 14 is selected from the group consisting of hydrogen, aryl, C 1 -C 6 alkyl, and C 1 -C 6 alkyl -COOR 6 ,
wherein aryl and alkyl being optionally substituted with one or more groups independently selected from R 15 ; and
R 15 is selected from the group consisting of hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, (CH 2 ) n′ C 3 -C 6 cycloalkyl, N(R 8 ) 2 , NR 8 S(O) 2 R 9 , NR 8 C(O) p R 9 , C(O)NR 8 R 9 , C(O) p R 8 , SR 8 , S(O) p R 8 and S(O) 2 NR 8 R 9 .
2. The compound claim 1 , wherein X and Y are respectively S and O; S and CH 2 ; or CH 2 and O.
3. The compound of claim 1 , wherein R 1 is C 3 -C 6 alkyl or (CH 2 ) n′ C 3 -C 6 cycloalkyl; R 2 and R 3 are each independently C 1 -C 3 alkyl; and r is 1.
4. The compound claim 3 , wherein X is positioned para to Y; and R 3 is positioned ortho to Y.
5. A compound having a structural Formula II,
or pharmaceutically acceptable salts or stereoisomers thereof,
wherein:
Q is: —C(O)OR 6 or R 6A ;
X is selected from the group consisting of a bond, CH 2 , O, S and S[O] p ;
Y is selected from the group consisting of a bond, S, CH 2 and O;
Z is benzothiopene;
wherein the benzothiophene is optionally substituted with one or more groups independently selected from R 15 ;
m and n′ are each independently selected from the group consisting of 0, 1, 2, 3 and 4;
n is selected from the group consisting of 0, 1, 2 and 3;
p is: 1 or 2;
r is selected from the group consisting of 1, 2, 3 and 4;
R 1 is selected from the group consisting of aryl,
haloalkyl,
C 1 -C 6 alkyl,
C 1 -C 6 alkyl-C 1 -C 6 alkoxy,
C 1 -C 6 alkyl-aryl,
C 2 -C 6 alkenyl,
C 2 -C 6 alkynyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
C 1 -C 6 alkoxy and
R 1 and R 2 together being a 5- to 8-membered heterocyclyl ring;
wherein alkyl, aryl, alkenyl, alkynyl, cycloalkyl and alkoxy being optionally substituted with one or more groups independently selected from R 15 ;
R 1a and R 1b are each independently selected from the group consisting of
hydrogen,
C 1 -C 6 alkyl, and,
R 1 and R 1a , R 1 and R 1b , R 2 and R 1a , R 2 and R 1b or R 1a and R 1b together being a 3- to 6-membered heterocyclyl or carbocyclyl ring where at least one of R 1a and R 1b is not hydrogen;
R 2 is selected from the group consisting of hydrogen,
haloalkyl,
C 1 -C 6 alkyl,
C 1 -C 6 alkyl-C 1 -C 6 alkoxy,
C 1 -C 6 alkyl-aryl,
C 2 -C 6 alkenyl,
C 2 -C 6 alkynyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
C 1 -C 6 alkoxy,
aryl, and
R 1 and R 2 together being a 5- to 8-membered heterocyclyl ring;
wherein alkyl, aryl, alkenyl, alkynyl, cycloalkyl and alkoxy being optionally substituted with one or more groups independently selected from R 15 ;
R 2a is selected from the group consisting of hydrogen, halo or C 1 -C 6 alkyl and wherein R 2 and R 2a together being a 3- to 8-membered ring; wherein alkyl being optionally substituted with one or more groups independently selected from R 15 ;
R 3 is selected from the group consisting of hydrogen,
halo,
cyano,
haloalkyl,
C 1 -C 6 alkyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
(C 1 -C 4 alkyl)-heterocyclyl, and
(C 1 -C 4 alkyl)-NR 7 C(O) p R 9 ;
wherein alkyl, cycloalkyl and heterocyclyl being optionally substituted with one or more groups independently selected from R 15 ;
R 4 and R 5 are each independently selected from the group consisting of hydrogen,
halo,
C 1 -C 6 alkyl
C 1 -C 6 alkoxy;
aryloxy;
N(R 8 ) 2 ,
SR 8 and
R 4 and R 5 together being a 3- to 8-membered ring;
R 6 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl and aminoalkyl;
R 6A is selected from the group consisting of carboxamide, C 1 -C 3 alkylnitrile, sulfonamide, acylsulfonamide and tetrazole;
R 7 is selected from the group consisting of hydrogen and C 1 -C 6 alkyl;
R 8 and R 9 are each independently selected from the group consisting of
hydrogen, C 1 -C 6 alkyl, aryl, heteroaryl, and heterocyclyl;
wherein aryl, heteroaryl and heterocyclyl being optionally substituted with one or more substituents selected from the group consisting of hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, oxo, C 1 -C 6 alkyl and C 1 -C 6 alkoxy;
R 15 is selected from the group consisting of hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, (CH 2 ) n′ C 3 -C 6 cycloalkyl, N(R 8 ) 2 , NR 8 S(O) 2 R 9 , NR 8 C(O) p R 9 , C(O)NR 8 R 9 , C(O) p R 8 , SR 8 , S(O) p R 8 and S(O) 2 NR 8 R 9 .
6. The compound of claim 5 , wherein X and Y are respectively S and O; S and CH 2 ; or CH 2 and O.
7. The compound of claim 6 , wherein R 1 is C 3 -C 6 alkyl or (CH 2 ) n′ C 3 -C 6 cycloalkyl; R 2 and R 3 are each independently C 1 -C 3 alkyl; and r is 1.
8. The compound claim 7 , wherein X is positioned para to Y; and R 3 is positioned ortho to Y.
9. The compound of claim 5 , wherein the compound having a structural Formula III,
or pharmaceutically acceptable salts or stereoisomers thereof, wherein:
n is: 1 or 2;
r is: 1, 2, 3, or 4;
X is: S or CH 2 ;
Y is: CH 2 or O;
Z is: benzothiophene;
wherein the benzothiophene is optionally substituted with one or more groups independently selected from R 15 ;
R 1 and R 2 are each independently selected from the group consisting of C 1 -C 6 alkyl and (CH 2 ) n′ C 3 -C 6 cycloalkyl; and
R 1a and R 1b , R 3 , R 4 and R 5 are each independently selected from the group consisting of hydrogen and C 1 -C 6 alkyl.
10. A compound having a structural Formula VI,
or pharmaceutically acceptable salts or stereoisomers thereof, wherein:
X is selected from the group consisting of a bond, CH 2 , O, S and S[O] p ;
Y is selected from the group consisting of a bond, S, CH 2 and O;
Z is benzothiophene; wherein the benzotihophene is optionally substituted with one or more groups selected from R 15 ;
n is: 0, 1, 2 or 3;
n′ is: 0, 1, 2, 3 or 4;
p is: 1 or 2;
r is: 1, 2, 3 or 4;
R 1 is selected from the group consisting of hydrogen,
haloalkyl,
C 1 -C 6 alkyl,
C 1 -C 6 alkyl-C 1 -C 6 alkoxy,
C 1 -C 6 alkyl-aryl,
C 2 -C 6 alkenyl,
C 2 -C 6 alkynyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
C 1 -C 6 alkoxy,
aryl, and
R 1 and R 2 together being a 5- to 8-membered heterocyclyl ring;
wherein alkyl, aryl, alkenyl, alkynyl, cycloalkyl and alkoxy being optionally substituted with one or more groups independently selected from R 15 ;
R 1a and R 1b are each independently selected from the group consisting of
hydrogen,
C 1 -C 6 alkyl, and
R 1 and R 1a , R 1 and R 1b , R 2 and R 1a , R 2 and R 1b or R 1a and R 1b together being a 3- to 6-membered heterocyclyl or carbocyclyl ring; wherein at least one of R 1a and R 1b is not hydrogen;
R 2 is selected from the group consisting of hydrogen,
haloalkyl,
C 1 -C 6 alkyl,
C 1 -C 6 alkyl-C 1 -C 6 alkoxy,
C 1 -C 6 alkyl-aryl,
C 2 -C 6 alkenyl,
C 2 -C 6 alkynyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
C 1 -C 6 alkoxy,
aryl, and
R 1 and R 2 together being a 5- to 8-membered heterocyclyl ring;
wherein alkyl, aryl, alkenyl, alkynyl, cycloalkyl and alkoxy being optionally substituted with one or more groups independently selected from R 15 ;
R 2a is selected from the group consisting of hydrogen, halo and C 1 -C 6 alkyl; wherein R 2 and R 2a together being a 3- to 8-membered ring; wherein alkyl being optionally substituted with one or more groups independently selected from R 15 ;
R 3 is selected from the group consisting of hydrogen,
halo,
cyano,
haloalkyl,
C 1 -C 6 alkyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
(C 1 -C 4 alkyl)-heterocyclyl, and
(C 1 -C 4 alkyl)-NR 7 C(O) p R 9 ,
wherein alkyl, cycloalkyl and heterocyclyl being optionally substituted with one or more groups independently selected from R 15 ;
R 6 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl and aminoalkyl;
R 7 is selected from the group consisting of hydrogen and C 1 -C 6 alkyl;
R 8 and R 9 are each independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, aryl, heteroaryl, and heterocyclyl;
wherein aryl, heteroaryl and heterocyclyl being optionally substituted with one or more substituents selected from the group consisting of hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, oxo, C 1 -C 6 alkyl and C 1 -C 6 alkoxy; and
R 15 is selected from the group consisting of hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, N(R 8 ) 2 , NR 8 S(O) 2 R 9 , NR 8 C(O) p R 9 , C(O)NR 8 R 9 , C(O) p R 8 , SR 8 , S(O) p R 8 and S(O) 2 NR 8 R 9 .
11. The compound of claim 10 , wherein the compound having a structural Formula VII,
or pharmaceutically acceptable salts or stereoisomers thereof,
wherein:
q is: 1, 2, 3, or 4;
T is S;
R 10 and R 11 are each independently selected from the group consisting of hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, C 1 -C 6 alkyl and C 1 -C 6 alkoxy;
wherein alkyl, aryloxy, and alkoxy being optionally substituted with one or more groups independently selected from R 15 .
12. The compound of claim 11 , wherein the compound having a structural Formula VIII,
or pharmaceutically acceptable salts or stereoisomers thereof,
wherein:
q is: 1 or 2;
R 1 is selected from the group consisting of C 3 -C 5 alky and (CH 2 ) n′ C 3 -C 6 cycloalkyl;
R 2 and R 3 are each independently: C 1 -C 3 alkyl;
R 10 is selected from the group consisting of halo, haloalkyl and C 1 -C 3 alkyl; wherein R 10 being substituted at a position 5, or 6, or both 5 and 6 of benzothiophenyl ring; and
R 11 is selected from the group consisting of hydrogen and C 1 -C 6 alkyl.
13. The compound of claim 12 , wherein R 10 is Cl, F, Br, CH 3 or CF 3 being substituted at a position 5 of benzothiophenyl ring.
14. A compound having a structural Formula IX,
or pharmaceutically acceptable salts or stereoisomers thereof, wherein:
E is selected from the group consisting of O, S and NR 14 ;
W is selected from the group consisting of
hydrogen, C 1 -C 6 alkyl, (CH 2 ) n′ C 3 -C 6 cycloalkyl, haloalkyl and acyl;
Q is selected from the group consisting of —C(O)OR 6 and R 6A ;
X is selected from the group consisting of a bond, C, O, S and S[O] p ;
Y is selected from the group consisting of a bond, S, CH 2 and O;
Z is benzothiopene: and:
wherein the benzothiophene is optionally substituted with one or more groups independently selected from R 15 ;
m and n′ are each independently: 0, 1, 2, 3 or 4;
n is: 0, 1, 2 or 3;
p is: 1 or 2;
r is: 1, 2, 3 or 4;
v is: 1 or 2;
R 1 is selected from the group consisting of hydrogen,
haloalkyl,
C 1 -C 6 alkyl,
C 1 -C 6 alkyl-C 1 -C 6 alkoxy,
C 1 -C 6 alkyl-aryl,
C 2 -C 6 alkenyl,
C 2 -C 6 alkynyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
C 1 -C 6 alkoxy,
aryl, and
R 1 and R 2 together being a 5- to 8-membered heterocyclyl ring:
wherein alkyl, aryl, alkenyl, alkynyl, cycloalkyl and alkoxy being optionally substituted with one or more groups independently selected from R 15 ;
R 1a and R 1b are each independently selected from the group consisting of
hydrogen,
C 1 -C 6 alkyl, and
R 1 and R 1a , R 1 and R 1b , R 2 and R 1a , R 2 and R 1b or R 1a and R 1b together being a 3- to 6-membered heterocyclyl or carbocyclyl ring wherein at least one of R 1a and R 1b is not hydrogen;
R 2 is selected from the group consisting of hydrogen,
haloalkyl,
C 1 -C 6 alkyl,
C 1 -C 6 alkyl-C 1 -C 6 alkoxy,
C 1 -C 6 alkyl-aryl,
C 2 -C 6 alkenyl,
C 2 -C 6 alkynyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
C 1 -C 6 alkoxy,
aryl, and
R 1 and R 2 together being a 5- to 8-membered heterocyclyl ring;
wherein alkyl, aryl, alkenyl, alkynyl, cycloalkyl and alkoxy being optionally substituted with one or more groups independently selected from R 15 ;
R 2a is selected from the group consisting of hydrogen, halo and C 1 -C 6 alkyl and wherein R 2 and R 2a together being a 3- to 8-membered ring; wherein alkyl being optionally substituted with one or more groups independently selected from R 15 ;
R 3 is selected from the group consisting of hydrogen,
halo,
cyano,
haloalkyl,
C 1 -C 6 alkyl,
(CH 2 ) n′ C 3 -C 6 cycloalkyl,
(C 1 -C 4 alkyl)-heterocyclyl, and
(C 1 -C 4 alkyl)-NR 7 C(O) p R 9 :
wherein alkyl, cycloalkyl and heterocyclyl being optionally substituted with one or more groups independently selected from R 15 ;
R 4 and R 5 are each independently selected from the group consisting of
hydrogen,
halo,
C 1 -C 6 alkyl
C 1 -C 6 alkoxy;
aryloxy;
N(R 8 ) 2 ,
SR 8 and
R 4 and R 5 together being a 3- to 8-membered ring;
R 6 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl and aminoalkyl;
R 6A is selected from the group consisting of carboxamide, C 1 -C 3 alkylnitrile, sulfonamide, acylsulfonamide and tetrazole;
R 7 is selected from the group consisting of hydrogen and C 1 -C 6 alkyl;
R 8 and R 9 are each independently selected from the group consisting of
hydrogen, C 1 -C 6 alkyl, aryl, heteroaryl, and heterocyclyl;
wherein aryl, heteroaryl and heterocyclyl being optionally substituted with one or more substituents selected from the group consisting of hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, oxo, C 1 -C 6 alkyl and C 1 -C 6 alkoxy;
R 14 is selected from the group consisting of hydrogen, aryl, C 1 -C 6 alkyl, and C 1 -C 6 alkyl -COOR 6 ;
wherein aryl and alkyl being optionally substituted with one or more groups independently selected from R 15 ; and
R 15 is selected from the group consisting of hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, oxo, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, (CH 2 ) n′ C 3 -C 6 cycloalkyl, N(R 8 ) 2 , NR 8 S(O) 2 R 9 , NR 8 C(O) p R 9 , C(O)NR 8 R 9 , C(O) p R 8 , SR 8 , S(O) p R 8 and S(O) 2 NR 8 R 9 .
15. The compound of claim 14 , wherein the compound having a structural Formula X:
and pharmaceutically acceptable salts, solvates, hydrates or stereoisomers thereof,
wherein:
n and q are each independently: 1, 2, 3 or 4;
T is S;
X is selected from the group consisting of CH 2 , O and S;
R 1 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl and (CH 2 ) n′ C 3 -C 6 cycloalkyl;
R 1a , R 1b , R 1c and R 2 are each independently selected from the group consisting of hydrogen and C 1 -C 6 alkyl; and
R 10 and R 11 are each independently selected from the group consisting of hydrogen, nitro, cyano, hydroxyl, halo, haloalkyl, haloalkyloxy, aryloxy, C 1 -C 6 alkyl and C 1 -C 6 alkoxy; wherein alkyl, alkoxy and aryloxy being optionally substituted with one or more groups selected from R 15 .
16. The compound of claim 15 , wherein the compound having a structural Formula XI:
or pharmaceutically acceptable salts or stereoisomers thereof, wherein:
q is 1 or 2;
E is selected from the group consisting of O, S and NR 14 ;
R 1 , R 2 and R 11 are each independently selected from the group consisting of C 1 -C 4 alkyl;
R 10 is selected from the group consisting of Cl, F, Br, CH 3 and CF 3 ; wherein R 10 being substituted at a position 5, or 6, or both 5 and 6 of benzothiophenyl ring; and
R 14 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl and aryl.
17. A compound selected from the group consisting of
No.
Structure
Name
1
3-(4-{2-[(5-Fluoro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- 2-methyl-phenyl)- propionic acid
2
3-(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- 2-methyl-phenyl)- propionic acid
5
3-(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-1-methyl-ethylsulfanyl}-2- methyl-phenyl)-propionic acid
6
(4-{2-[(5-Chloro-3- ethyl-benzo[b]thiophene-2- sulfonyl)-propyl amino]-1-methyl- ethylsulfanyl}-2- methyl-phenoxy)-acetic acid
7
4-{2-[(6-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- 2-methyl-phenoxy)-acetic acid
8
4-{2-[(7-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- 2-methyl-phenoxy)-acetic acid
9
(4-{2-[(4-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- 2-methyl-phenoxy)-acetic acid
10
(4-{2-[(5-Chloro-3- trifluoromethyl- benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- 2-methyl-phenoxy)-acetic acid
11
(4-{2-[(5-Chloro-3- trifluoromethyl- benzo[b]thiophene-2- sulfonyl)-propyl- amino]-1-methyl- ethoxy}-2-methyl- phenoxy)-acetic acid
13
2-(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propy]- amino]-ethyl}- phenoxy)-2-methyl- propionic acid
14
2-(4-{3-[(3,5-Dimethyl- benzo[b]thiophene-2- sulfonyl)-propyl- amino]-propyl}- phenoxy)-2-methyl- propionic acid
15
2-(4-{3-[(5-Fluoro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-propyl}- phenoxy)-2-methyl- propionic acid
16
2-(4-{3-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-(2,2,2- trifluoro-ethyl)-amino]- propyl}-phenoxy)-2- methyl-propionic acid
17
2-(4-{2-[(3-Ethyl- benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethoxy}-3- propyl-phenoxy)-2- methyl-propionic acid
18
2-[4-(1-{[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-methyl}- propoxy)-2-methyl- phenoxy]-2-methyl- propionic acid
19
3-[4-(1-{[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-methyl}- propoxy)-2-methyl- phenyl]-propionic acid
20
[4-(1-{[(5-Fluoro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-methyl}- propylsulfanyl)-2- methyl-phenoxy]-acetic acid
21
[4-(1-{[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-methyl}- propylsulfanyl)-2- methyl-phenoxy]-acetic acid
22
[4-(1-{[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-methyl}- propylsulfanyl)-2- methyl-phenoxy]-acetic acid
34
(R)-(2-Methyl-4-{1- methyl-2-[(3-methyl-5- trifluoromethyl- benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- phenoxy)-acetic acid
35
(R)-3-(4-{2-[(6-Chloro- 5-fluoro-3-methyl- benzo[b]thiophene-2- sulfonyl)-propyl- amino]-1-methyl- ethylsulfanyl}-2- methyl-phenyl)-propionic acid
36
(R)-(4-{2-[(6-Chloro-5- fluoro-3-methyl- benzo[b]thiophene-2- sulfony])-propyl- amino]-1-methyl- ethylsulfanyl}-2- methyl-phenoxy)-acetic acid
79
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- 2-propyl-phenoxy)-acetic acid
80
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- phenoxy)-acetic acid
81
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- 2-trifluoromethyl- phenoxy)-acetic acid
83
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propy]- amino]-1-methyl- ethylsulfanyl}-2- methyl-phenoxy)-acetic acid
84
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-1-methyl- ethylsulfanyl}-2- methyl-phenoxy)-acetic acid
85
(2-Methyl-4-{2-[(3- methyl-5-trifluoromethyl- benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- phenoxy)-acetic acid
90
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- 2-methyl-phenoxy)-acetic acid
91
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-(3-methyl- butyl)-amino]- ethylsulfanyl}-2- methyl-phenoxy)-acetic acid
92
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-cyclopropyl- amino]-ethylsulfanyl}- 2-methyl-phenoxy)-acetic acid
93
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-cyclobutyl- amino]-ethylsulfanyl}- 2-methyl-phenoxy)-acetic acid
94
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-cyclopropylmethyl- amino]-ethylsulfanyl}- 2-methyl-phenoxy)-acetic acid
95
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-pentyl-amino]- ethylsulfanyl}-2- methyl-phenoxy)-acetic acid
96
(4-{2-[Butyl-(5-chloro- 3-methyl-benzo[b]thiophene-2- sulfonyl)-amino]- ethylsulfanyl}-2- methyl-phenoxy)-acetic acid
98
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethoxy}-2- methyl-phenylsulfanyl)- acetic acid
99
(4-{3-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-propyl}-2- methyl-phenoxy)-acetic acid
100
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-1-methyl- ethoxy}-2-methyl- phenoxy)-acetic acid
101
3-(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl-amino]-1- methyl-ethoxy}-2-methyl- phenyl)-propionic acid
102
2-(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-1-methyl- ethoxy}-2-methyl- phenoxy)-2-methyl- propionic acid
103
3-(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-1-methyl- ethoxy}-2-methoxy- phenyl)-propionic acid
104
(4-{2-[(5-Fluoro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-1-methyl- ethylsulfanyl}-2- methyl-phenoxy)-acetic acid
105
3-(4-{2-[(5-Fluoro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-1-methyl- ethoxy}-2-methyl- phenyl)-propionic acid
106
(4-{2-[(5-Fluoro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-1-methyl- ethoxy}-2-methyl- phenoxy)-acetic acid
107
(2-Chloro-4-{2-[(5- chloro-3-methyl- benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- phenoxy)-acetic acid
108
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl)- 2-ethyl-phenoxy)-acetic acid
112
(R)-(3-Chloro-4-{2-[(5- chloro-3-methyl- benzo[b]thiophene-2- sulfonyl)-propyl-amino]-1- methyl-ethylsulfanyl}-phenyl)- acetic acid
113
(3-Chloro-4-{2-[(5- chloro-3-methyl- benzo[b]thiophene-2- sulfonyl)-propyl- amino]-ethylsulfanyl}- phenyl)-acetic acid
114
[4-(1-{[(5-Fluoro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-methyl}- propoxy)-2-methyl- phenoxy]-acetic acid
115
3-[4-(1-{[(5-Fluoro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-methyl}- propoxy)-2-methyl- phenyl]-propionic acid
116
3-(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-butoxy}-2- methyl-phenyl)-propionic acid
117
[4-(1-{[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-methyl}- propoxy)-2-methyl- phenoxy]-acetic acid
118
[4-(1-{[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-methyl}- propoxy)-2-methoxy- phenoxy]-acetic acid
119
(4-{2-[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-phenethyl- amino]-ethylsulfanyl}- 2-methyl-phenoxy)- acetic acid
120
(4-{2-[Benzyl-(5- chloro-3-methyl- benzo[b]thiophene-2- sulfonyl)-amino]- ethylsulfanyl}-2- methyl-phenoxy)-acetic acid
121
[4-(1-{[(5-Chloro-3- methyl-benzo[b]thiophene-2- sulfonyl)-propyl- amino]-methyl}- propylsulfanyl)-2- methyl-phenoxy]-acetic acid.
18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound of claim 1 or pharmaceutically acceptable salts thereof.
19. A method for lowering blood-glucose in a mammal comprising the step of administering an effective amount of at least one compound of claim 1 .Cited by (0)
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